Exoantigens are produced by pathogenic and nonpathogenic trypanosomes such as Trypanosoma brucei and T. lewisi, respectively. These antigens elicit a protective, trypanocidal response, but there is some evidence that the exoantigens of T. lewisi are also involved in the ablastic response, a reproduction-inhibiting immunity that distinguishes the nonpathogenic from the pathogenic African trypanosomes. It is proposed to establish with certainty whether the exoantigens of T. lewisi are involved in the ablastic response and then to make a detailed comparative study of the exoantigens of pathogenic and nonpathogenic trypanosomes produced in a single host species. The latter phase will center on characterization of the exoantigens including association with host serum proteins, physical separation, molecular size and chemical nature; cross reactions between the exoantigens in vivo and in vitro; the role of exoantigens in induction of host anemia; and the relation of exoantigens to the surface coat of the parasites. Through this comparative approach, it may be possible to learn why an ablastic response fails to develop against the pathogenic trypanosomes. Furthermore, the proposed study will increase our basic knowledge of the biology of these parasites and may reveal significant differences that could lead to effective control measures against the African trypanosomes.